Leptin, adiponectin, and ghrelin levels in female patients with asthma during stable and exacerbation periods.

OBJECTIVE: The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma. METHODS: We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy. RESULTS: Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV(1)/FVC and FEF(25-75) in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased. CONCLUSION: Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity.

Fetuin-A is associated with disease severity and exacerbation frequency in patients with COPD.

Fetuin-A is a liver protein that may serve as an inhibitor of systemic inflammation in humans. In the present study we assessed the levels of fetuin-A in COPD patients in stable condition and on exacerbation in an attempt to evaluate it as a clinically relevant biomarker that may serve as predictor of exacerbations of COPD (ECOPD). One hundred COPD outpatients (GOLD stage I to IV) were enrolled in a tertiary University hospital and were submitted to a detailed evaluation, including pulmonary function testing, exercise capacity, quality of life and evaluation of the presence of metabolic syndrome and serum CRP. All patients were followed-up for 1 year, and 36 were re-evaluated at the onset of an ECOPD. Forty otherwise healthy smokers served as controls. Serum fetuin-A levels were reproducible at baseline, 6 and 12 months. COPD patients presented lower levels of fetuin compared to controls [394.5 (321.8-419.6) vs. 487.3 (441.0-548.0) mg/L, p < 0.001]. COPD patients with GOLD stage IV had lower fetuin-A levels compared to stages I-II and III (p < 0.05). Fetuin-A was significantly reduced at the onset of an ECOPD compared to baseline (p < 0.001) and the time to the first ECOPD significantly different between patients with high and low levels of fetuin-A [HR 2.163 (95%CI 1.104-4.238), p = 0.024). The results of the present study suggest that fetuin-A is a reproducible and clinically relevant biomarker in patients with COPD that may be useful in the identification of exacerbation-prone patients.

Association of bone mineral density, parameters of bone turnover, and body composition in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) often develop osteoporosis. Many hormones regulate bone metabolism and body composition, and some of them are affected in COPD patients vs controls. In 46 COPD patients, we measured hip neck, total hip, lumbar spine, and whole-body T-score with dual-energy X-ray absorptiometry, parameters of body composition (body mass index [BMI], fat mass index [FMI], and fat-free mass index [FFMI]), and adiponectin, leptin, parathormone, osteocalcin, calcitonin, and insulin-like growth factor I (IGF-I) serum levels and correlated them with COPD stage. Our results suggest that total hip bone mineral density (BMD) is affected by FFMI and COPD stage; lumbar spine BMD is affected by FMI and COPD stage; and whole-body BMD is affected by BMI, COPD stage, and leptin. Adiponectin, parathormone, osteocalcin, calcitonin, and IGF-I levels were not significantly correlated to BMD at any of the measured sites. Our findings are in agreement with the current literature in that a decline in lung function is correlated to a decline in BMD.

Diagnostic accuracy of biomarkers of oxidative stress in parapneumonic pleural effusions.

BACKGROUND: The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF(2α)) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. METHODS: The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. RESULTS: Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58·1% at a cut-off point of 35·1 (AUC = 0·848). CONCLUSIONS: Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas.

Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers.

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.

Statins and outcome after hospitalization for COPD exacerbation: a prospective study.

BACKGROUND: Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking. METHODS: We followed-up prospectively 245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly evaluations for one year. The role of statins on outcomes was evaluated by Cox regression analysis after proper adjustments for age, gender, BMI, current smoking status, Charlson comorbidity index and COPD stage. Health-related quality of life (HRQoL) was evaluated by Saint George's Respiratory Questionnaire. RESULTS: There was no effect of statins on either 30-day or 1-year mortality. Patients receiving statins presented a lower total number of ECOPD during the 1-year follow up (2.1 ± 2.7 vs. 2.8 ± 3.2 ECOPD/patient respectively, p = 0.037). After proper adjustments, the use of statins was associated with a lower risk for ECOPD [HR: 0.656 (95% CI: 0.454-0.946)] and severe ECOPD [HR: 0.608 (95%CI: 0.381-0.972)]. The group of statins presented better improvement in HRQoL at 2, 6 and 12 months (p < 0.001). CONCLUSIONS: The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL. These data support a possible beneficial role for these agents in COPD.

The association of metabolic syndrome with adipose tissue hormones and insulin resistance in patients with COPD without co-morbidities.

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome represent common causes of morbidity and mortality in ageing populations. The effect of the co-existence of COPD and metabolic syndrome on adipose tissue hormones and insulin resistance as well as the differences between COPD patients with and without metabolic syndrome have not been adequately studied. The prevalence of metabolic syndrome, based on Adult Treatment Panel III (ATP III) criteria, was evaluated in 114 male patients with COPD without significant co-morbidities. Pulmonary functions tests (PFTs), arterial blood gases, quality of life and BODE index were assessed. Blood samples were obtained for the assessment of adipose tissue hormones and insulin resistance. The overall prevalence of metabolic syndrome was 21%, being more prevalent in earlier stages of COPD. Patients with COPD and metabolic syndrome were younger with higher body-mass index (BMI), had better pulmonary function, less static hyperinflation and air-trapping, better diffusing capacity for carbon monoxide and BODE index. These patients had higher levels of leptin, lower levels of adiponectin and increased insulin resistance, as expressed by HOMA index, compared with patients without metabolic syndrome. Metabolic syndrome was more prevalent in younger patients with less severe COPD. These patients may constitute a specific COPD phenotype with greater leptin to adiponectin imbalance and insulin resistance, despite smaller impairment in PFTs. The prognosis and differences of these patients compared with other COPD phenotypes needs to be determined in prospective studies.

Prevalence of chronic diseases and morbidity in primary health care in central Greece: an epidemiological study.

BACKGROUND: In Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care. METHODS: Four primary health centres were randomly selected. During one year period, 12 visits were performed in each centre, one per month, in random order and all visitors willing to participate in the study were included. Data on morbidity of each subject were recorded after performing an interview with the participant and checking his medical records, medical history and current medication. Diseases were coded using the international classification of primary care (ICPC) system. RESULTS: In total 20,299 subjects were recorded. The results revealed significant variations in morbidity between genders and age groups. However, in all age groups, diseases of the circulatory system were most prevalent, followed by endocrine, metabolic, musculoskeletal and respiratory diseases. Osteoporosis was significantly more prevalent in females compared to males, whereas skin and eye disorders were more prevalent in subjects below 65 years old. COPD prevalence was very low compared to worldwide data. CONCLUSIONS: The present study revealed great variations in the prevalence of the diseases between genders and age groups. Our data justify the urgent need for the development of electronic health records that may help in the design of new prevention strategies in primary health care.

COPD prevalence and the differences between newly and previously diagnosed COPD patients in a spirometry program.

AIMS: To evaluate the prevalence and severity of COPD in a primary care population participating in a spirometry program. Differences between newly and previously diagnosed COPD patients were identified. METHODS: A spirometry program was conducted in 15 primary care centres. Visitors aged over 30 years who were willing to perform spirometry were included in this program. RESULTS: A total of 1,526 subjects provided acceptable spirometries. COPD prevalence in our population was 18.4%, of whom 69.0% were newly diagnosed. Most patients were classified as GOLD stages I and II (26.0% and 54.0%, respectively). COPD diagnosis was related to gender (men), age (older subjects), history of repeated respiratory infection in childhood, smoking (>10 pack-years) and presence of symptoms (cough, dyspnoea, wheezing). Variables related to newly diagnosed COPD were younger age and absence of chronic cough. CONCLUSIONS: A primary care spirometry program may identify a large proportion of undiagnosed COPD patients especially in the early stages of the disease. Newly diagnosed COPD patients were of younger age and presented with less symptoms. These results support the need for spirometry programs in primary care for early COPD detection.

Association of TLR4-T399I polymorphism with chronic obstructive pulmonary disease in smokers.

Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.

Epidemiological and clinical aspects of human brucellosis in Central Greece.

The confirmed cases of human brucellosis in the area of Larissa in Central Greece from 2003 to 2005 were analyzed to assess the features of the affected population and to determine the factors influencing the acquisition of infection. Data of patients infected by Brucella spp. concerning age, gender, occupation, date of diagnosis and the observed symptoms were collected from regional hospitals, health centres and private practitioners. The incidence of human brucellosis in the area was 32.49 cases/100,000 inhabitants. Males, due to their professions, were affected more often by brucellosis than females. The majority of the cases were attributed to direct contact with animals or their products. Only in 8.49% of the cases was the infection attributed to the consumption of dairy products. The urban population is not at potential risk for acquiring brucellosis because all commercialized dairy products in Greece are produced from pasteurized milk. The occurrence of human brucellosis shows seasonality, with the majority of the cases diagnosed from December to May. Direct contact with animals, the season of the year and gender were the risk factors influencing the acquisition of infection. Fever, arthralgia, profuse sweating and anorexia were the symptoms most often observed.

Clinical phenotypes related to smoking cessation.

INTRODUCTION: The aim of the current study is the identification of clinical phenotypes of patients visiting a specialized smoking cessation center and the determination of smoking cessation rate for each phenotype, 1 year after the initial evaluation. METHODS: Seven hundred eighty-three smokers who visited the outpatient clinic were included in the study. Demographic data, smoking habits, tobacco dependence and comorbidities were recorded. Smoking cessation rates and carbon monoxide levels were determined 1 year after the initial evaluation. RESULTS: The overall smoking cessation rate 1 year after the initial evaluation was 32.3%. Four distinct phenotypes were identified. The first one included mainly young women with low tobacco dependence and allergic profile. The second and the third ones included mainly men with high tobacco dependence, without comorbidities, treated with varenicline and bupropione SR, respectively. The fourth one included mainly older men with high tobacco dependence and smoking related comorbidities. Smoking cessation rates for each phenotype were 33.8, 39.4, 23.3, and 24.6%, respectively. CONCLUSION: Patients visiting a specialized smoking cessation center can be categorized in different phenotypes. Phenotyping may lead to a more personalized approach concerning smoking cessation.

Predicting short-term mortality in patients with pulmonary embolism: a simple model.

BACKGROUND: The aim of the present study was to develop a simple prognostic rule that could classify patients with pulmonary embolism (PE) into categories of increased risk of 30-day mortality. METHODS: One hundred patients with PE were enrolled. Clinical and laboratory findings were recorded on admission for each patient. Differences between groups' survival and death were tested, and the association with the 30-day mortality was determined. RESULTS: Three variables had a significant effect on survival: age, Charlson index and the alveolar to arterial (A-a) gradient. A receiver operating characteristic analysis was performed, and the cut-off points used for the comparison of survival were 67 years of age, A-a gradient over 52.8 mm Hg and Charlson index over 2. By combining these variables, a score was established for distinguishing patients with PE who are at high risk. This score was also validated in a group of 30 consecutive patients admitted to the hospital for PE Additionally, a tree method was applied and showed that for patients with a history of diabetes and Charlson index >3, the expected outcome is death. CONCLUSIONS: The results of this study suggest that patients with PE could be stratified into categories of increasing risk of 30-day mortality using a simple score based only on routinely available variables. Future studies are needed to validate our prognostic model in a large cohort of patients with PE.

Secondhand smoke exposure induces acutely airway acidification and oxidative stress.

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p < 0.001) and returned to baseline by 180 min, whereas H(2)O(2) increased at 120 min and remained increased at 240 min (p = 0.001). No changes in exhaled NO and NO(2)/NO(3) were observed, while decreases in FEV(1) (p < 0.001) and FEV(1)/FVC (p < 0.001) were observed after exposure and returned to baseline by 180 min. A 1-h exposure to secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28.

Two-year mortality of patients with COPD in primary health care: an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a significant cause of morbidity and mortality, with high rates of underdiagnosis. There are no studies about following up COPD patients in primary health care. The aim of the current study was to estimate two-year mortality for COPD patients in primary care and assess the parameters associated with mortality. METHODS: A total of 263 patients with a new COPD diagnosis were followed up for two years. Follow-up included phone contacts every six months for assessment of vital status, and re-examination visits every year after the initial diagnosis. Visits included performance on spirometry, assessment of smoking status, evaluation of adherence with treatment, and assessment of the number of exacerbations during the previous year. RESULTS: One hundred and eighteen patients with COPD completed the study. The overall mortality was 27.9%. Most patients had quit smoking two years after the initial diagnosis, whereas the percentage of patients showing high adherence with treatment was 68%. Parameters associated with two-year mortality were age and coronary heart disease comorbidity. CONCLUSION: The mortality of patients with COPD in primary care remains significantly high, whereas adherence with treatment remains significant low. Age, smoking status, and a history of depression are major determinants of mortality in primary health care.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer.

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Five-year trends of second-hand smoke exposure in Greece: a comparison between complete, partial, and prelegislation levels.

BACKGROUND: Our aim was to assess second-hand smoke (SHS) exposure in hospitality venues after the smoke-free legislation implemented in September 2010 in Greece and to compare with when a partial ban was in place and in 2006 when no ban was in place. METHODS: Hospitality venues were prospectively assessed for their indoor concentrations of particulate matter (PM(2.5)) during the partial ban phase (n=149) and the complete ban phase (n=120, 80% followed up), while overall and matched by venue comparisons were also performed (no ban vs. partial ban vs. complete ban). Comparisons with previously collected data in 2006 when no ban was in place also was performed. RESULTS: Indoor air levels of PM(2.5) attributable to SHS dropped following the transition from a partial to a complete ban by 34% (137 µg/m(3) vs. 90 µg/m(3), p=0.003). This drop was larger in bars (from 195 µg/m(3) to 121 µg/m(3)), than in cafes (124 µg/m(3) vs. 87 µg/m(3)) or restaurants (42 µg/m(3) vs. 39 µg/m(3)). PM(2.5) concentrations between 2006 (no ban) and the partial ban of 2010 were also found to decrease by 94 µg/m(3); however, among matched venues, the levels of indoor air pollution were not found to change significantly (218 µg/m(3) vs. 178 µg/m(3), p=0.58). Comparing the 2010 complete ban results (n=120) with previously collected data from 2006 when no ban was in place (n=43), overall PM(2.5) concentrations were found to fall from 268 µg/m(3) to 89 µg/m(3), while a matched analysis found a significant reduction in PM(2.5) concentrations (249 µg/m(3) vs. 46 µg/m(3), p=0.011). CONCLUSION: The complete ban of smoking in hospitality venues in Greece led to a reduction in SHS exposure, in comparison to when the partial ban or no ban was in place; however, exposure to SHS was not eliminated indicating the need for stronger enforcement.

Comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis.

BACKGROUND: Early diagnosis of Chronic Obstructive Pulmonary Disease (COPD) remains the cornerstone for effective management. In this study we compared an open spirometry programme and a case-finding programme providing spirometry to high-risk subjects selected by primary care physicians. METHODS: A network of primary care physicians was created after invitation and all participants received training on COPD and spirometry. The study team visited 12 primary care settings in each programme in a 1-year period. Spirometry was performed in all eligible participants. COPD diagnosis and classification was based on GOLD guidelines and evaluation by a chest physician. RESULTS: Patients with acceptable spirometry were evaluated (n = 201 in the case-finding and n = 905 in the open spirometry programme). The proportion of newly diagnosed COPD was 27.9% in the case-finding programme compared to 8.4% in the open spirometry programme (p < 0.0001). The number needed-to-screen (NNS) for a new diagnosis of COPD was 3.6 in the case-finding programme compared to 11.9 in the open spirometry programme. The majority of newly diagnosed patients were classified in GOLD stages I an II. The average cost for a new diagnosis of COPD was 173 € in the open spirometry programme and 102 € in the case-finding programme. CONCLUSIONS: A case-finding programme involving primary care physicians was more cost-effective for the identification of new cases of COPD compared to an open spirometry programme. The development of networks of primary care physicians with access to good quality spirometry and specialist consultation for early diagnosis of COPD is justified.

Exhaled NO and exhaled breath condensate pH in the evaluation of asthma control.

BACKGROUND: Asthma is a chronic inflammatory airways disorder. However, no biomarker of airways inflammation has been included in the assessment of asthma control. OBJECTIVE: To evaluate exhaled NO (FeNO) and exhaled breath condensate (EBC) pH in patients with asthma according to the level of control, and their performance in the identification of not well-controlled patients. METHODS: FeNO and EBC pH after Argon deaeration were measured in 274 consecutive patients. Asthma control was evaluated by two asthma specialists blinded to FeNO and pH measurements according to GINA guidelines, as well as by asthma control test (ACT) and asthma control questionnaire (ACQ). RESULTS: FeNO was higher and EBC pH was lower in patients with not well-controlled compared to controlled asthma. In ROC analysis, FeNO presented an AUC of 0.790 for the identification of not well-controlled asthma performing better in non-smokers; EBC pH presented an AUC of 0.791 for the identification of not well-controlled asthma, performing better in smokers. The performance of both biomarkers was inferior to that of ACT and ACQ. FeNO values >30 ppb presented positive predictive values (PPV) > 0.85 with the exception of smokers treated with inhaled corticosteroids. EBC pH values ≤7.20 presented PPV >0.80 in all groups. The presence of FeNO >30 ppb and/or EBC pH ≤7.20 was indicative of not well-uncontrolled asthma in 88.3% of the patients. CONCLUSION: FeNO and EBC pH levels may identify patients with not well-controlled asthma. However, their performance was inferior to clinical judgment and may be limited to selected subgroups of asthmatic patients.

Body composition in severe refractory asthma: comparison with COPD patients and healthy smokers.

BACKGROUND: Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated. METHODOLOGY AND PRINCIPAL FINDINGS: 213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3-18.3)-19.5(18.4-21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I-III COPD and comparable to those of stage IV COPD patients [18.0(17.3-18.3)-18.8(17.8-20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used. CONCLUSIONS AND SIGNIFICANCE: SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.